D. Böhringer

The effects of cidofovir 1% with and without cyclosporin a 1% as a topical treatment of acute adenoviral keratoconjunctivitis: a controlled clinical pilot study

OBJECTIVE To evaluate the efficacy of cidofovir 1% eyedrops with and without cyclosporin A 1% eyedrops as a treatment of acute adenoviral keratoconjunctivitis (AKC). DESIGN Randomized, controlled trial. PARTICIPANTS Thirty-four patients with acute adenoviral keratoconjunctivitis of recent onset. METHODS Patients were divided into 4 treatment groups: 1) cidofovir four times daily, 2) cidofovir 10 times daily, 3) cidofovir four times daily and cyclosporin A four times daily, and 4) sodium chloride four times daily (control). The diagnosis was confirmed by adenoviral polymerase chain reaction from conjunctival swabs. Duration of treatment was 21 days. MAIN OUTCOME MEASURES Severity of conjunctival injection, conjunctival chemosis, punctate epithelial keratitis during the course of treatment, and presence and severity of corneal subepithelial infiltrates were evaluated by a clinical score. Duration until subjective improvement of symptoms was recorded. RESULTS The frequency of severe corneal opacities was lower with cidofovir (P = 0.048). Cidofovir was toxic locally to the skin of the eyelids and the conjunctiva in a dose-dependent manner. Symptoms of local toxicity were clinically similar to the signs of the initial viral inflammation. They first appeared 8 to 12 days after beginning of treatment and completely subsided 7 to 28 days after discontinuation of cidofovir. The outcome measures of local inflammation did not differ between the four treatment groups. Cyclosporin A did not alter the course of the infection. CONCLUSIONS Cidofovir lowers the frequency of severe corneal opacities, but its clinical use 4 to 10 times daily at a 1% concentration is limited by local toxicity. Further clinical studies to find an efficacious yet tolerable dosage regimen of cidofovir, possibly using an improved pharmaceutical preparation, are required.

HLA class I and II matching improves prognosis in penetrating normal-risk keratoplasty.

BACKGROUND HLA matching in penetrating keratoplasty is still neglected in most eye clinics. This is due to contradictory results of studies performed in the past. Different surgical techniques in multicenter studies, missing risk differentiation in high-risk situations and faulty HLA typing can be identified as the main reasons for these contradictory results. In this monocenter study, the value of HLA class I and II matching (A, B, DR loci) was examined in a homogenous group of 398 normal-risk keratoplasty patients using modern typing techniques. METHODS Penetrating normal-risk keratoplasty was performed in two groups of patients (group I with 0-2, group II with 3-6 mismatches in the A/B/DR loci). Surgery was done by 3 experienced surgeons according to a standardized scheme. Also, postoperative therapy and controls were standardized. There were no statistically significant differences between the two study groups as regards number of AB0 or H-Y compatibilities, patient age, patient gender, ratio of previous intraocular surgery, ratio of triple procedures, indication for surgery, follow-up period, donor age, donor gender, post-mortem time of the graft and endothelial cell density of the graft at the end of organ culture. HLA typing was performed in a quality-controlled laboratory, serologically for HLA class I (A and B loci) and moleculargenetically for HLA class II (DR locus). RESULTS Four years postoperatively, the ratio of clear and rejection-free graft survival was 91% in group I and 67% in group II (Kaplan-Meier estimation, log rank test, p = 0.03). Monovariate analysis in the Cox model gave no influence of solitary HLA class I or II matching, but only an influence of combined HLA class I and II matching (p = 0.03). CONCLUSIONS In this monocenter study with proper typing techniques the beneficial effect of HLA class I plus II matching on clear and rejection-free graft survival could be demonstrated in a homogenous group of normal-risk keratoplasty patients.

Costs and Financing

PURPOSE To estimate the averaged cost of processing a corneal graft for keratoplasty. METHODS We estimated the total running costs of a German corneal bank for one year. All procurement-related expenses were calculated on the basis of 300 donors per year and a disavowal percentage of 50%. RESULTS The running costs comprise of personnel (2 physicians, 2 technicians), amortization of equipment, laboratory costs, laboratory consumables, occupancy costs and quality management. Annual expenses total 584000 EUR. This aggregation divided by 300 corneal grafts released for transplantation results in a nominal charge of 1950 EUR per corneal graft. DISCUSSION The DRG system in Germany (in-patients at a base rate of 1.0) refunds only 850 EUR, leaving a financial gap of 1100 EUR per keratoplasty. This financial burden is currently left over to the eye bank and/or the surgeon.

HLA B27 seems to promote graft failure following penetrating keratoplasties for herpetic corneal scars

BACKGROUND Herpes simplex virus (HSV) is the leading cause of infectious corneal blindness in the developed world. Eighty percent of the general population develop asymptomatic viral latency in the trigeminal ganglion following orofacial inoculation, but only 0.2% of all such orofacial inoculations are followed by recurrent corneal reactivation. Recurrences still threaten graft survival following penetrating keratoplasty, so that advance identification of patients at increased risk would be helpful in aftercare following penetrating keratoplasty. The HLA B27 phenotype is associated with increased susceptibility to genital HSV. However, no such association has been reported for herpetic eye disease. METHODS The HLA phenotypes of 129 patients who underwent penetrating keratoplasties for herpetic corneal scars were available for retrospective analysis. Four of these patients were positive for HLA-B27. The 125 HLA-B27-negative patients served as controls. The mean follow-up was 2.2 years. We compared the frequencies of herpetic recurrence and graft failure in the two groups using the Kaplan-Meier method and applied log-rank statistics. RESULTS After the average period of follow-up, 75% (three patients) of the HLA B27-positive patients experienced either graft failure or at least one reversible recurrence of the herpetic eye disease, as against only 25% of controls. This difference was highly statistically significant (p<0.01). CONCLUSION This retrospective analysis suggests that the HLA B27 phenotype promotes recurrence of herpetic eye disease following penetrating keratoplasty. HLA B27-positive patients should be closely monitored, and the indications for prophylactic antiviral therapy should be viewed liberally in this group.

Individual Analysis of Expected Time on the Waiting List for HLA-Matched Corneal Grafts

OBJECTIVE Recent studies report the beneficial effect of HLA matching for long-term prognosis of penetrating keratoplasty (kp). This improvement of prognosis, however, has to be weighed against the additional time on the waiting list due to the search for a HLA-compatible graft. Reliable estimation of this additional waiting period is a prerequisite for informed consent on the waiting policy. METHODS A mathematical model based on survival analysis and HLA haplotype frequencies was used to estimate time on the waiting list for each of 1,400 HLA-typed patients registered at the Lions Cornea Bank NRW. Additionally, the waiting period of each patient was retrospectively determined. Both values were tested for correlation. This analysis was performed for acceptance of up to two mismatches on HLA-A, -B and -DR. RESULTS When accepting two, one and zero mismatches, median predicted waiting period was 1 +/- 6, 7 +/- 49 and 17 +/- 159 months respectively. Median waiting period in retrospective simulation was 1 +/- 3, 5 +/- 9 and 15 +/- 14 months. Correlation of values from the predictive formula and simulation was statistically significant (p < 0.0001). CONCLUSION Predicted time on the waiting list is a valuable tool for management of HLA matching in kp.

[Perforating keratoplasty versus Descemet stripping automated endothelial keratoplasty in the partner eye: Functional results and patient satisfaction].

BACKGROUND This study compared the postoperative results and patient satisfaction between penetrating keratoplasty (PK) and Descemet stripping automated endothelial keratoplasty (DSAEK) in patients who underwent PK in one eye and DSAEK in the other eye. METHODS A total of 15 patients were identified from the corneal database register and the medical charts were analyzed for best corrected visual acuity (BCVA), keratometric astigmatism, endothelial cell density and postoperative complications. Patient satisfaction was evaluated by a standardized interview. RESULTS Median follow-up time for PK was 55 months and 18 months for DSAEK (p < 0.01). Median BCVA in PK was 0.8 and 0.5 in DSAEK (p = 0.01) at the end of follow-up. Median keratometric astigmatism was 3.1 diopters after PK and 1.9 diopters after DSAEK (p = 0.2). Median endothelial cell density was 831 cells/mm(2) after PK and 860 cells/mm(2) after DSAEK (p = 0.63). For the interventions 57 % of the patients preferred PK, 36 % preferred DSAEK and 7 % were undecided. Patients assigned the better performing eye to the PK side in 64 % and in 29 % to the DSAEK side and 7 % perceived equal visual performance in both eyes. CONCLUSION The results leave doubt about the superiority of DSAEK compared to PK; however, exceptionally good refractive results of the 15 PK eyes analyzed and significantly longer follow-up times after PK could be the reason for the unexpectedly high patient preference for PK.

Perforierende Keratoplastik vs. „Descemet stripping automated endothelial keratoplasty“ im Partnerauge

BACKGROUND This study compared the postoperative results and patient satisfaction between penetrating keratoplasty (PK) and Descemet stripping automated endothelial keratoplasty (DSAEK) in patients who underwent PK in one eye and DSAEK in the other eye. METHODS A total of 15 patients were identified from the corneal database register and the medical charts were analyzed for best corrected visual acuity (BCVA), keratometric astigmatism, endothelial cell density and postoperative complications. Patient satisfaction was evaluated by a standardized interview. RESULTS Median follow-up time for PK was 55 months and 18 months for DSAEK (p < 0.01). Median BCVA in PK was 0.8 and 0.5 in DSAEK (p = 0.01) at the end of follow-up. Median keratometric astigmatism was 3.1 diopters after PK and 1.9 diopters after DSAEK (p = 0.2). Median endothelial cell density was 831 cells/mm(2) after PK and 860 cells/mm(2) after DSAEK (p = 0.63). For the interventions 57 % of the patients preferred PK, 36 % preferred DSAEK and 7 % were undecided. Patients assigned the better performing eye to the PK side in 64 % and in 29 % to the DSAEK side and 7 % perceived equal visual performance in both eyes. CONCLUSION The results leave doubt about the superiority of DSAEK compared to PK; however, exceptionally good refractive results of the 15 PK eyes analyzed and significantly longer follow-up times after PK could be the reason for the unexpectedly high patient preference for PK.

Perforierende Keratoplastik mit Transplantaten pseudophaker Spender

ZusammenfassungHintergrund. Eine Pseudophakie wird bislang als relatives Ausschlusskriterium für eine Hornhautspende angesehen. Ziel dieser retrospektiven Studie war es, den klinischen Verlauf nach perforierender Keratoplastik mit Hornhäuten pseudophaker Spender zu erfassen. Patienten und Methoden. Von April 1996 bis Juli 2000 erhielten 16 Patienten im Rahmen perforierender Keratoplastiken Transplantate pseudophaker Spender (Gruppe I). Als Kontrollgruppe (Gruppe II) dienten 26 Patienten, die in demselben Zeitraum Transplantate nichtpseudophaker Hornhautspender erhielten. Ausgewertet wurde im Hinblick auf das klare Transplantatüberleben, den Anteil der Transplantate ohne Immunreaktion sowie das Ausmaß des Endothelzellverlustes. Ergebnisse. In der Nachbeobachtungszeit von knapp einem Jahr wurden bei keinem der 16 Patienten in Gruppe I Transplantatversagen oder Immunreaktionen beobachtet. In der Gruppe II waren in demselben Zeitraum noch 90% der Transplantate klar und 91% frei von Immunreaktionen (Kaplan-Meier-Schätzung). Im Log-rank-Test waren die Unterschiede zwischen den beiden Studiengruppen nicht signifikant. Die Patienten in Gruppe I verloren postoperativ durchschnittlich 0,86±0,82 Zellen pro mm2 und Tag im Vergleich zu 1,4±1,8 Zellen pro mm2 und Tag in Gruppe II. Dieser Unterschied war im t-Test für unverbundene Stichproben statistisch nicht signifikant. Schlussfolgerung. Eine kritische Endothelevaluation vorausgesetzt, sollte eine Pseudophakie, die sich bei potenziellen Spendern zunehmend häufig findet, nicht grundsätzlich als Ausschlusskriterium für eine Hornhautspende angesehen werden.AbstractPurpose. Pseudophacia is considered to be a relative exclusion criterion for cornea donation. The aim of this retrospective study was to investigate the clinical outcome and prognosis of penetrating keratoplasty with grafts from pseudophacic donors. Patients and methods. From April 1996 to July 2000 16 patients received grafts from pseudophacic donors (group I). The control group (group II) comprised 26 patients with grafts from donors without a history of intraocular surgery. Graft survival, ratio of grafts without immune reactions and chronic endothelial cell loss were compared between both groups. Results. During a follow-up of almost 1 year, no graft failures and no graft rejections were observed in group I. In group II 90% of the grafts remained clear and 91% of the grafts remained free of immune reactions in the same follow-up period (Kaplan-Meier estimation). The differences between the study groups were not statistically significant. Chronic endothelial cell loss was 0.86±0.82 cells per mm2 and day in group I and 1.4±1.8 cells per mm2 and day in group II. This difference was not statistically significant. Conclusion. Our clinical results reveal no reason to regard pseudophacia as a principal contraindication for cornea donation, provided a critical endothelial evaluation is carried out.

Perforierende Keratoplastik vs. „Descemet stripping automated endothelial keratoplasty“ im Partnerauge@@@Perforating keratoplasty versus Descemet stripping automated endothelial keratoplasty in the partner eye: Funktionelle Ergebnisse und Patientenzufriedenheit@@@Functional results and patient satisfaction

BACKGROUND This study compared the postoperative results and patient satisfaction between penetrating keratoplasty (PK) and Descemet stripping automated endothelial keratoplasty (DSAEK) in patients who underwent PK in one eye and DSAEK in the other eye. METHODS A total of 15 patients were identified from the corneal database register and the medical charts were analyzed for best corrected visual acuity (BCVA), keratometric astigmatism, endothelial cell density and postoperative complications. Patient satisfaction was evaluated by a standardized interview. RESULTS Median follow-up time for PK was 55 months and 18 months for DSAEK (p < 0.01). Median BCVA in PK was 0.8 and 0.5 in DSAEK (p = 0.01) at the end of follow-up. Median keratometric astigmatism was 3.1 diopters after PK and 1.9 diopters after DSAEK (p = 0.2). Median endothelial cell density was 831 cells/mm(2) after PK and 860 cells/mm(2) after DSAEK (p = 0.63). For the interventions 57 % of the patients preferred PK, 36 % preferred DSAEK and 7 % were undecided. Patients assigned the better performing eye to the PK side in 64 % and in 29 % to the DSAEK side and 7 % perceived equal visual performance in both eyes. CONCLUSION The results leave doubt about the superiority of DSAEK compared to PK; however, exceptionally good refractive results of the 15 PK eyes analyzed and significantly longer follow-up times after PK could be the reason for the unexpectedly high patient preference for PK.

HLA B27 scheint Transplantatversagen nach Hornhautverpflanzung bei herpetischen Hornhautnarben zu fördern@@@HLA B27 seems to promote graft failure following penetrating keratoplasties for herpetic corneal scars

BACKGROUND Herpes simplex virus (HSV) is the leading cause of infectious corneal blindness in the developed world. Eighty percent of the general population develop asymptomatic viral latency in the trigeminal ganglion following orofacial inoculation, but only 0.2% of all such orofacial inoculations are followed by recurrent corneal reactivation. Recurrences still threaten graft survival following penetrating keratoplasty, so that advance identification of patients at increased risk would be helpful in aftercare following penetrating keratoplasty. The HLA B27 phenotype is associated with increased susceptibility to genital HSV. However, no such association has been reported for herpetic eye disease. METHODS The HLA phenotypes of 129 patients who underwent penetrating keratoplasties for herpetic corneal scars were available for retrospective analysis. Four of these patients were positive for HLA-B27. The 125 HLA-B27-negative patients served as controls. The mean follow-up was 2.2 years. We compared the frequencies of herpetic recurrence and graft failure in the two groups using the Kaplan-Meier method and applied log-rank statistics. RESULTS After the average period of follow-up, 75% (three patients) of the HLA B27-positive patients experienced either graft failure or at least one reversible recurrence of the herpetic eye disease, as against only 25% of controls. This difference was highly statistically significant (p<0.01). CONCLUSION This retrospective analysis suggests that the HLA B27 phenotype promotes recurrence of herpetic eye disease following penetrating keratoplasty. HLA B27-positive patients should be closely monitored, and the indications for prophylactic antiviral therapy should be viewed liberally in this group.